Changes in blood oxygen saturation are of pivotal importance in a multitude of clinical conditions, including peripheral vascular disease, congenital cardiac abnormalities, diabetes, hypoxemias such as in chronic obstructive pulmonary disease, and ischemic disease of various organs. Current noninvasive methods are based on near infrared spectroscopy (NIRS) which can measure tissue oxygen saturation. These methods, however, are hampered by poor resolution. Further, the relative opacity of mammalian tissue to optical radiation precludes measurements of deep-lying tissues, and the method is unable to target specific arteries and veins. Quantitative MRI resting on a measurement of blood T2 has proven useful but the method requires extensive calibration and its implementation is involved. In this project we propose the development, implementation and validation of a new method for measuring blood oxygen saturation that involves virtually no calibration, allows for rapid and reliable measurement of hemoglobin saturation in arteries and veins at high spatial resolution. The method's principle is based on a measurement of the bulk magnetic susceptibility of blood, which is a function of the blood's hemoglobin oxygen saturation. In a vessel that can be modeled as a cylinder whose diameter is much less than its length, the demagnetizing field has a simple closed-form solution. From the intra-to-extravascular induced magnetic field difference obtained by phase mapping, the blood's volume susceptibility can be computed and thus hemoglobin saturation obtained. We show in preliminary work the method's feasibility and demonstrate its ability to quantify the response to a physiologic stimulus in the peripheral circulation. In four specific aims we propose to further develop and evaluate the image acquisition and processing methodology and quantify potential sources of error, both computationally and experimentally. We plan to validate the method in human subjects in models of peripheral limb ischemia and compare the baseline and post-occlusion hyperemic response with those of blood gas analysis as well as with tissue oxygen saturation measured by NIRS. PUBLIC HEALTH RELEVANCE: Venous and arterial oxygen saturation are among the most important physiological parameters. Currently, there exist no robust noninvasive techniques for measuring hemoglobin saturation in individual deep-lying vessels. Magnetic resonance susceptometry has substantial promise to fill this gap. [unreadable] [unreadable] [unreadable]